Last week, FDA published a final guidance in which it provided medical device makers with details on its interpretation of section 522 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which grants FDA the authority to require that manufacturers of certain class II and III devices conduct postmarket surveillance. The document, entitled “Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act,” will replace FDA’s April 2006 guidance, entitled “Guidance for Industry and FDA Staff; Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act.”

Postmarket Surveillance Plans

Once a 522 order has been issued, it will be assigned a postmarket surveillance (PS) number (PS######). This PS number should be cited by manufacturers when submitting the proposed postmarket surveillance plan. If the 522 order contains multiple requirements, a separate plan should be submitted for each one. The postmarket surveillance plan must be submitted to FDA within 30 days of receipt of the 522 order, and surveillance must begin within 15 months. FDA will review and respond to all submissions within 60 calendar days.

Elements of a Postmarket Surveillance Submission

Most postmarket surveillance submissions should include the following elements:

Patient population (including subject inclusion and exclusion criteria and definition and source of comparator group)

Sample size calculation (statistically justified and based on study hypothesis, where applicable)

Primary and secondary endpoints (including definitions for endpoints, success criteria, a list of expected adverse events/complications, an agreement to collect unexpected adverse events, and a plan to assess relatedness of endpoints with the device and/or the procedure)

Length of follow-up, follow-up schedule, description of baseline, and follow-up assessments, where applicable

Expected date of initiation of subject enrollment expected number of subjects enrolled per month

Expected date for subject enrollment completion

Expected date to complete follow-up of all study participants

If applicable, information related to intermediate milestones (e.g., evaluation of surrogate endpoints in a study that also measures clinical benefits)”

FDA & Manufacturer Agreement on Surveillance Plan

“FDA will evaluate the proposed surveillance plan to determine whether it is administratively complete and whether the plan will result in the collection of useful data that will answer the surveillance questions.” At this point, the Agency may issue one of the following decision letters:

Not Acceptable Letter

Approval Letter

Minor Deficiency Letter

Major Deficiency Letter

Disapproval Letter

If the manufacturer does not agree with the Agency’s decision, possible recourse options are available, as described in 21 CFR 822.22.

Changes to an Approved Postmarket Surveillance Plan

If a device maker seeks to change an approved postmarket surveillance plan in a way that will affect the nature or validity of the data, the manufacturer must request and obtain written approval from the FDA before making such changes. The request should be submitted as a standalone supplement, rather than with any other 522 report(s). Any supplements that are submitted should be identified by the assigned PS number.

“Unless FDA approves the revised surveillance plan, the manufacturer remains responsible for completing the approved surveillance plan. Failure to meet the milestones and timelines outlined in the approved surveillance plan may result in enforcement action by FDA.”

Types of Postmarket Surveillance

According to the guidance, “FDA may order postmarket surveillance to address a wide variety of device-related public health questions.” As such, the guidance document contains a lengthy list of different postmarket surveillance designs that may be used. For additional information, view the full guidance.

Interim Postmarket Surveillance Reports

An Interim Postmarket Surveillance Report “is a written report to FDA on the status of the fulfillment of a postmarket surveillance requirement prior to its completion.” Manufacturers should submit Interim Postmarket Surveillance Reports every six months for the first two years of surveillance. At the conclusion of the initial two-year period, manufacturers will only need to submit Interim Postmarket Surveillance Reports once each year. In its guidance, FDA states that it “intends to complete the review of interim reports and respond within 60 calendar days.”

Final Postmarket Surveillance Reports

“A Final Postmarket Surveillance Report is a written report of a terminated 522 order requirement or a completed postmarket surveillance.” This report must be submitted within three months after the completion of surveillance, and should be clearly identified as the Final Postmarket Surveillance Report at the top of the cover letter.

FDA will review and respond to manufacturers’ submissions within 90 days of receipt. At this time, if the Agency concludes that the manufacturer has fulfilled all obligations of the 522 order, the manufacturer will receive a letter reflecting that decision. “However, if the results of the postmarket surveillance raise new issues or questions, additional actions may be required.”

“Failure or refusal to comply with a requirement under section 522, including failure to commence surveillance within 15 months of a 522 order, is a prohibited act under section 301(q)(1)(C) of the Act, 21 U.S.C. § 331(q)(1)(C), and renders the device misbranded under section 502(t)(3) of the Act, 21 U.S.C. § 352(t)(3). Please note that violations of sections 301(q)(1)(C) and 502(t)(3) may lead to enforcement actions including seizure of product, injunction, prosecution, and/or civil money penalties.”

Do you manufacture a medical device or other FDA-regulated product? We can help ensure that your product is compliant with all of the Agency’s requirements. To learn more about our services and how we can help you, contact us today.